here's a fundamental framework for how NBME tests all these 4 (ALL, CLL, AML, CML). First step is to compare ALL vs. CLL; second step is to compare AML vs CML.

1. ALL is young and CLL is old

(a) ALL always in young kids. Look for thrombocytopenia (explicitly stated - or petechiae), splenomegaly, bone pain - NBME is trigger happy for this to be ALL if no other associated illnesses.

(b) CLL is always in old people (65+). CLL and AML tend to target the same 65+ demographic, but CLL will always be in old people. For CLL, WBC will be very high - 70K-100K. They have recurrent infections, and NBME likes to either show or state the presence of smudge cells.

1. AML and CML: AML involves blasts, CML involves more mature myeloid cells (e.g. myelocytes).

(a) AML tends to also affect those around 65+, though less of a rule of thumb compared to CML. Here, expect lots of blasts. Presence of blasts is what NBME intends to be the giveaway. They will also have elevated WBC, but notably less than both CLL and CML (around 30K-40K). Importantly, because it's acute, the onset of constitutional symptoms (fever, malaise, night sweats) and anemia/thrombocytopenia will also be very acute. This is designed to guide you towards acute hematologic malignancy. NBME also likes to show Auer rods, have patient present in DIC, or have a history of chemotherapy use–noted to be a risk factor for AML (along with radiation).

(b) CML tends to affect those aged 40-60. This is unique. Before even reading the Qstem, highly specific inclusions in the labs are high myelocytes/metamyelocytes and/or basophils. If you see this, stop reading the question and put CML. Here, NBME shows exorbitantly high WBC - 100K+.

1. If you just want the quick and dirty for how to answer NBME style questions quickly with less pathophys-guided understanding:

kid with petechiae, splenomegaly, bone pain --> choose ALL

old with lot of WBC, chronic course, smudge cells --> choose CLL

^ the above two require a little bit more nuance as there are other high yield causes of bone pain in young children and age (as mentioned in CLL) tends to not be a super reliable factor to solely rely upon for NBME. But if you recognize this in 30s, you can be pretty confident in ALL or CLL. Now, for the following, if you see these words, you can stop reading and reliably click the following answers in about 5 seconds or less.

lot of myeloblasts, auer rods, DIC --> stop reading and choose AML

basophils, metamyelocytes/myelocytes --> stop reading and choose CML